In recent years we have developed many spontaneously metastasizing rat mammary carcinomas with various metastatic potentials in the inbred strain of W/Fu rats. These tumors encompass the entire spectrum of metastatic situations observed in human cancer, and also have many of the biological, biochemical and immunological characteristics of human carcinomas. They invade directly into the surrounding stroma and metastasize via the lymphatics, are nonimmunogenic, and shed soluble, organ-specific glycoprotein antigen from the cell surface into their microenvironment in rough proportion to their metastasizing capacity. Such antigen is detected in the sera of rats as early as one week after implantation of the tumor, even before the graft is palpable, and its level rises with the growth of tumor. Utilizing this tumor system, we plan to study the biochemical and immunological mechanisms of metastasis, antigen shedding and the effect of shed antigen on the host immune system. We also plan to study the mechanism of selective anti-tumor and anti-metastatic response of athymic nude mice against the graft of these metastasizing rat tumors, while the same T-cell deficient immunological milieu accepting and promoting the growth of syngeneic nonmetastasizing, highly immunogenic rat tumors.